Denaturing gradient gel electrophoresis (DGGE) is being utilized to screen for mutations in candidate disease genes. In psychiatric disorders, we are scanning dopamine receptor genes. In proliferative disorders, GTPase activating protein (GAP) is involved in the regulation of normal ras proteins through its catalytic domain, and plays a role in the signal transduction pathway of some growth factors. We screened several tumor types for mutations in GAP. We have found mutations in the SH2 region of GAP, which regulates signal transduction, in basal cell carcinomas. A new technology of scanning molecules for mutations spectrophotometrically is being developed. Linkage analysis of manic depressive illness has been investigated by using a set of 57 microsatellite marker loci. Multiplexing techniques were employed for PCR and electrophoresis. We found isolated LOD scores on chromosome 1 greater than 2 in individual pedigrees, but analysis of the series for linkage with heterogeneity did not give significance. Results o simulations show that when the disease locus is not linked to any of the marker loci, there is still a considerable probability of observing at leas one lod score greater than 2.